This project is concerned with the nature of specific antigen recognition by thymus-derived or T lymphocytes. We are currently using a variety of techniques to study the following points: 1. What is the antigenic complex recognized by T cells? Our data currently indicate a precise recognition of three elements: a chemically defined antigenic determinant, or hapten; its protein carrier; and self histocompatibility antigens encoded in the I region of the major histocompatibility complex. We are currently trying to demonstrate that it is the first and last of these that is important to T cells, and that the recognition of carrier is at the level of the macrophage. 2. How do macrophages and lymphocytes communicate with one another? It would appear that each sequesters some of its specifically interacting molecules until such time as the two cells come into contact, whereupon full expression takes place. However, developing evidence that this is so is difficult. 3. What determines which antigen associates with which self cell surface marker? We have a system using lipid-modified antigens that appear to associate selectively with I region molecules. We are now trying to definitively demonstrate this, and then to determine why it takes place. 4. What other self structures are recognized by T cells? We are working on a model system in which self immunoglobulin may be recognized by T cells, which are involved in the fine regulation of antibody responses by immunoglobulin-bearing B cells.